We propose a pilot project in which we will initiate DNA linkage studies for pedigrees of familial Alzheimers disease that have been identified by the Clinical Core of the Alzheimers Disease Research Center proposed for Baylor College of Medicine, This Core has already diagnosed many affected patients, a significant number of whom come from families with evidence for inheritance of the disease. This population represents a valuable resource that should be explored to enhance our understanding of the disease. In addition, since molecular understanding and diagnosis of Alzheimers is clearly imminent, it is also important that a laboratory able to provide state-of-the-art services to the Clinical Core and its patients be established as soon as possible. We will evaluate case records to select 15 to 20 families with the best evidence of Alzheimers inheritance and availability of persons required for such investigations. Initial molecular studies will test linkage between inheritance of the disease and loci on chromosome 21 known to be near a gene associated with a form of the disease having an early age of onset. As other markers are identified they will be applied to the analysis of our kindreds. We anticipate that this pilot project will lead to the establishment of a continuing research program at Baylor College of Medicine for the molecular analysis of Alzheimers disease, the identification of kindreds that will be valuable resources for enhancing our understanding of Alzheimers disease, and the provision of molecular services to local patients.